Long promised, a lifelong vaccine for every form of influenza has entered human trials.

This article was created for the Icahn School of Medicine at Mount Sinai, in New York City, by Scientific American Custom Media, a division separate from the magazine’s board of editors.

October 19, 2018

The Universal Flu Shot Moves Within ReachAdolfo García-Sastre (left), Professor of Microbiology and Medicine and Director of the Global Health and Emerging Pathogens Institute at the Icahn School of Medicine, is working to develop a universal flu vaccine. Credit: Mount Sinai Health System

For most people, getting a flu shot ranks just below dental visits and spring cleaning on the list of annoying annual chores. If Peter Palese, Adolfo García-Sastre, and Florian Krammer have their way, it could be taken off the list entirely.

Palese is the Horace W. Goldsmith Professor of Medicine (Infectious Diseases) and Professor and Chair of the Department of Microbiology at the Icahn School of Medicine at Mount Sinai, and he and his colleagues are developing a universal flu vaccine that, he says, “would protect against all different variants of the influenza virus, and would offer long-lasting or even lifelong protection.”

That would be no mean feat.

“There are four branches of influenza virus that are changing: two influenza A strains and two B strains,” says Palese. “As a result of this constant change, each year there is a different influenza vaccine, containing either three or four components; and every year, at least one will change.”Image of the influenza virus. Credit: Mount Sinai Health System

How is it possible to protect against a virus that doesn’t yet exist? By looking for the parts that don’t change, says García-Sastre, Professor of Microbiology and Medicine (Infectious Diseases) and Director of the Global Health and Emerging Pathogens Institute at the Icahn School of Medicine.

“The current vaccine is actually very good at inducing response to the variable regions of the virus,” says García-Sastre. “But there are other parts of the structure of the virus that remain unchanged, or conserved. Our idea for the universal vaccine is to induce antibodies against the conserved areas.”

The flu virus resembles a ball with little mushrooms sprouting all over it; the mushroom-shaped proteins are called hemagglutinin, and they are responsible for helping the virus particle bind to and fuse with the targeted human cells. “Each hemagglutinin protein has a head and a stalk. What we realized is that the changes, or variability, occur on the head,” says Palese. “The stalk of the protein is more stable, so we are making antibodies against the stalk.”

With recent advances in genome sequencing, the team was able to more clearly assess the molecular structure of influenza’s various surface proteins, including hemagglutinin. “Taking advantage of techniques developed at Mount Sinai, in particular, about the reverse genetics of influenza viruses, we were able to synthesize in the laboratory vaccine constructs,” Palese says. “When given to different animal models, those induced long-lasting protective immune responses against different influenza challenge viruses.”

García-Sastre, Palese, and Krammer, an Associate Professor of Microbiology at the Icahn School of Medicine, are now testing their vaccine in phase I/II clinical trials. “The first thing we need to demonstrate is that there are no adverse effects,” García-Sastre says. “The second thing we need to prove is efficacy—that the vaccine is effective not only against the current strains, but others, including future strains.”

Another effort, funded by a grant from the Bill & Melinda Gates Foundation and conducted in collaboration with the global health research organization PATH, is placing a live-attenuated vaccine into a phase I trial that Palese, Krammer, and García-Sastre helped design. “Whereas we are mostly working with an inactivated vaccine, in which the virus has been grown in embryonated eggs and then killed, the trial funded by the Gates Foundation uses a different platform: a live-attenuated vaccine, which delivers pathogens that are still alive but weakened,” says Palese. “While the CDC recommends inactivated vaccine for most population groups, the live-attenuated vaccine is cheaper to produce and deliver—and less painful. Instead of being injected with a needle, this vaccine would be delivered via a nasal spray.”

How close is the universal flu vaccine to becoming reality? “Our initial findings are promising, but we still need to conduct phase II and phase III trials,” says García-Sastre. “Hopefully, the vaccine could be ready in five years.”

Whenever it arrives, García-Sastre says, “The impact of a universal influenza virus vaccine will be enormous. Influenza is one of the biggest killers in the world, taking between 291,000 and 646,000 lives a year, and during pandemic years, it is even worse. A universal flu vaccine could reduce the huge costs associated with responding to and treating influenza; and most importantly, it could save millions of lives.”

Universal Flu Vaccine can go the way of Polio Vaccine like said in Jurassic Park movie, " “Life breaks free. Life expands to new territories. Painfully, perhaps even dangerously. But life finds a way” Viruses find a way just like life.

Polio has been gone for lots of years but look: "So far this year, 127 confirmed or suspected cases of acute flaccid myelitis, or AFM, have been reported to the Centers for Disease Control and Prevention — a significant increase over 2017 and a worrying perpetuation of a disease for which there is little understanding."

Enterovirus 68 (EV68, EV-D68, HEV68) is a member of the Picornaviridae family, an enterovirus. First isolated in California in 1962 and once considered rare, it has been on a worldwide upswing in the 21st century. With some uncertainty, it has been implicated in cases of a polio-like disorder called acute flaccid myelitis.

So do not celebrate a Universal Flu Vaccine because we do not know what it will truly bring on. If this Polio like illness from entrovirus 68 spreads we will be back we bill be back 70 years pre Polio vaccine days.

"Be carful what you wish for it may not be what you wanted." Dr. Spock, Star Trek

Please keep in mind that polio vaccine saved hundreds of thousands of lives and immeasurable human agony over decades. There will always be new diseases that step forward for which there is little immediate defense. However, a universal flu vaccine could save millions of lives if a severe flu pandemic were to occur. Believe me, current flu vaccines would still leave us virtually defenseless and be far too little, far too late.

It is actually possible to eradicate a virus. To do so requires a very effective vaccine, intelligent - co-ordinated application and an almost complete uptake rate. Political will is needed, alongside the science.

Smallpox is extinct in the wild. It only remains in the lab. This was achieved by a detailed WHO co-ordinated international program.

To do this for flu would be a million times harder, as it has so many non-human reservoirs (birds, pigs etc.) but it could be done. I can't see it happening, as people are even harder ro herd than cats, but it is possible - in theory.

So assuming we fail, or never attempt this*, it will find a way around the vaccine eventually. In the meantime it will save many lives.

We constantly hear about "progress" The vaccine has only been 5 years away my entire adult life. Of course I am skeptical.

Technophobe you are right to some degree however, as far as I can tell all the viruses that have been eradicated are human only viruses. Small pox was relatively easy to eradicate because there is no known animal reservoir. Once you stopped the spread in humans it went away. Even if we eliminate it from the human population it will keep spreading among the animals and will make a come back in the future at some point.

If there is a universal vaccine that is proved both safe and effective I would probably get it.

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